Ajai Chari, MD, on the FDA’s Concern About CAR-T Increasing the Likelihood of T-Cell Malignancies

At the 65th American Society of Hematology Annual Meeting & Exposition, Dr. Chari, Professor of Clinical Medicine and Director of the Myeloma Program at the University of California, San Francisco, reflects on the US Food and Drug Administration (FDA) investigating the risk of patients developing T-cell malignancies following chimeric antigen receptor (CAR) T-cell therapy.

“It’s important that we start with the fact that a lot of these CAR-Ts got approved under what we call an accelerated approval single-arm strategy,” Dr. Chari began. “When you have a single-arm strategy, these products are very efficacious.”

Dr. Chari emphasized that if patients develop side effects from CAR-T, it’s difficult to tell whether they are coming from patient factors, the nature of the disease itself, or the treatment.

“In single-arm studies, you can’t isolate the true causative factor,” he said. “To do that, you need randomized, controlled studies, and those are ongoing.”

Dr. Chari mentioned that only one of 600 patients with myeloma had a T-cell malignancy after CAR-T. “It turns out that T-cell abnormality was actually detectable even before the CAR-T,” he said. “We don’t need to raise alarms about a T-cell malignancy that was likely already at a prodromal state in the patient before they got CAR-T, fludarabine, or cyclophosphamide.”

Dr. Chari also mentioned that the FDA requires 15 years of follow-up, which he noted is a testament to how active these therapies are.

“I’m not worried about this,” he said. “It’s likely not going to change the risk-benefit profile of most of these approved products…but I do think we need to study this more.”